Dietary Regulation of Gut-Brain Axis in Alzheimer’s Disease: Importance of Microbiota Metabolites

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease that impacts 45 million people worldwide and is ranked as the 6th top cause of death among all adults by the Centers for Disease Control and Prevention. While genetics is an important risk factor for the development of AD, environment and lifestyle are also contributing risk factors. One such environmental factor is diet, which has emerged as a key influencer of AD development/progression as well as cognition. Diets containing large quantities of saturated/trans-fats, refined carbohydrates, limited intake of fiber, and alcohol are associated with cognitive dysfunction while conversely diets low in saturated/trans-fats (i.e., bad fats), high mono/polyunsaturated fats (i.e., good fats), high in fiber and polyphenols are associated with better cognitive function and memory in both humans and animal models. Mechanistically, this could be the direct consequence of dietary components (lipids, vitamins, polyphenols) on the brain, but other mechanisms are also likely to be important. Diet is considered to be the single greatest factor influencing the intestinal microbiome. Diet robustly influences the types and function of micro-organisms (called microbiota) that reside in the gastrointestinal tract. Availability of different types of nutrients (from the diet) will favor or disfavor the abundance and function of certain groups of microbiota. Microbiota are highly metabolically active and produce many metabolites and other factors that can affect the brain including cognition and the development and clinical progression of AD. This review summarizes data to support a model in which microbiota metabolites influence brain function and AD.

Mapping trends and hotspot regarding gastrointestinal microbiome and neuroscience: A bibliometric analysis of global research (2002–2022)

“…In addition, numerous experts in microbiology and neuroscience from Ireland, China, the United States, and other countries have studied the characteristics of the gastrointestinal microbiota in health and neuroscience disease states, the connection between pathological function and neuroscience disease, and other topics. These professionals, who serve as a foundation for the creation and publication of papers in this area, include Cryan JF, Dinan TG, Clarke G, Stanton C, O’Mahony SM, Bastiaanssen TFS, Yang C, Xie P, Bailey MT, Green SJ, Keshavarzian A, and Forsyth CB ( Clarke et al, 2013 ; Dinan et al, 2014 ; Mayer et al, 2014 ; Stilling et al, 2015 ; Tarr et al, 2015 ; Dodiya et al, 2020 ; Joers et al, 2020 ; Li et al, 2020 ; van de Wouw et al, 2020 ; Frausto et al, 2021 ; Zheng et al, 2021 ; Connell et al, 2022 ; Teng et al, 2022 ). It is worth noting that the citations of articles published in the United States rank first, followed by Ireland and China.…”

Comprehensive characterization of multi-omic landscapes between gut-microbiota metabolites and the G-protein-coupled receptors in Alzheimer’s disease

“…Much effort in the field has been devoted to developing therapeutics based on targeting disease-modifying modalities or genetic factors in AD. However, thus far over 99% of clinical trials have failed 75 , highlighting the heterogenous etiopathology and pathogenesis of AD. Thus, there is an urgent need to uncover potential targets from a chemical perspective.…”

Gut-Brain Axis and Food

“…An animal-based diet can increase bile-tolerant microbiota like Bacteroides, bilophila, and alistipes but can decrease firmicutes [48]. High saturated/trans-fat, low fiber, and refined carbohydrate diet can contribute to cognitive dysfunction, and even development and progression of Alzheimer's disease, possibly through the microbiota metabolites [49].…”